60719-84-8 Usage
Description
Amrinone, also known as inamrinone, is a selective cAMP phosphodiesterase (PDE-3) inhibitor with positive inotropic and vasodilatory activity. It is a positive inotropic agent useful in the management of severe congestive heart failure, even in unresponsive, fully digitalized patients. Amrinone is a crystalline solid that increases developed tension and contractile force in isolated cat papillary muscle, enhancing the rate and force of heart contraction in anesthetized and unanesthetized dogs.
Uses
Used in Cardiotonic Applications:
Amrinone is used as a cardiotonic agent for its ability to increase intracellular calcium levels in the heart, which in turn improves cardiac contractility. It achieves this by inhibiting the degradation of cAMP, an essential molecule in regulating calcium channels and storage sites for calcium in the heart.
Used in Treatment of Cardiac Insufficiency:
Amrinone is used for the short-term treatment of cardiac insufficiency that does not respond to treatment with other drugs. It is particularly effective in managing severe congestive heart failure, even in patients who have not responded to digitalization.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Amrinone is used as an active pharmaceutical ingredient in the development of drugs for the treatment of heart failure and other related cardiovascular conditions. Its unique mechanism of action as a PDE-3 inhibitor makes it a valuable compound in the search for more effective heart failure treatments.
Originator
Sterling-Winthrop (USA)
Manufacturing Process
A mixture containing 10g of 3-nitro-5-(4-pyridinyl)-2(1H)-pyridinone, 200 ml
of dimethylformamide and 1.5 g of 10% palladium-on-charcoal was
hydrogenated under pressure (50 psi) at room temperature until the uptake of
hydrogen ceased (about 30 minutes). The reaction mixture was filtered
through infusorial earth and the filtrate was heated in vacuum to remove the
solvent. The residual material was crystallized from dimethylformamide,
washed successively with ethanol and ether, and dried in a vacuum oven at
80°C for 8 hours to yield 6 g of 3-amino-5-(4-pyridinyl)-2(1H)-pyridinone,
melting point 294° to 297°C with decomposition.
Therapeutic Function
Cardiotonic
Safety Profile
Poison by ingestion andintravenous routes. Human systemic effects by ingestion:cardiac arrhythmias, liver function, thrombocytopenia. Anexperimental teratogen. Other experimental reproductiveeffects. When heated to decomposition it emits toxicfumes o
Synthesis
Amrinone, 3-amino-5-(4-piridinyl)-2(1H)-pyridinone (17.2.4), can be synthesized
from piridine-4-acetic acid, the reaction of which with a mixture of diemthylformamide—
phosphorous oxychloride gives 2-(4-piridyl)-3-dimethylaminoacrolein (17.2.1).
Reacting this with cyanoacetamide gives 3-cyano-5-(4-piridyl)-2(1H)-pyidinone (17.2.2).
Hydrolysis of the cyano group of this product gives 3-carbamyl-5-(4-piridyl)-2(1H)-pyidinone
(17.2.3). A Hofmann rearrangement of this product (using bromine in sodium
hydroxide) gives amrinone (17.2.4).
An alternative method for the synthesis of amrinone from 3-cyano-5-(4-piridyl)-2(1H)-
pyridinone (17.2.2) is based on it’s acidic hydrolysis to the corresponding acid, 3-carboxy-
5-(4-piridyl)-2(1H)-pyridinone (17.2.5), nitration of which with nitrous acid in the presence
of sulfuric acid forms 3-nitro-5-(4-piridyl)-2(1H)-pyridinone (17.2.6). Reducing the nitro
group of this product with hydrogen gives the desired amrinone (17.2.4).
Check Digit Verification of cas no
The CAS Registry Mumber 60719-84-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,0,7,1 and 9 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 60719-84:
(7*6)+(6*0)+(5*7)+(4*1)+(3*9)+(2*8)+(1*4)=128
128 % 10 = 8
So 60719-84-8 is a valid CAS Registry Number.
InChI:InChI=1/C10H9N3O/c11-9-5-8(6-13-10(9)14)7-1-3-12-4-2-7/h1-6H,11H2,(H,13,14)
60719-84-8Relevant articles and documents
Synthesis of a stable pyridyl boronate and its reaction with aryl and heteroaryl halides
Durrant, Steven J.,Pinder, Joanne L.,Charrier, Jean-Damien,Jimenez, Juan-Miguel,Brenchley, Guy,Collier, Philip N.,Kay, David,Miller, Andrew,Pierard, Francoise,Ramaya, Sharn,Sadiq, Shazia,Twin, Heather C.
, p. 509 - 517 (2008/02/02)
The synthesis and reaction of a versatile 5-pyridyl boronate is described. This intermediate can be used to synthesize a range of biologically interesting 2-(1H)-pyridones.
N-Hydroxy-1,2-dihydro-2-oxo-5-(pyridinyl)-nicotinimidamide and their cardiotonic use
-
, (2008/06/13)
N-Hydroxy-1-R1 -1,2-dihydro-2-oxo-5-PY-6-R-nicotinimidamides or pharmaceutically-acceptable acid-addition salts thereof, useful as cardiotonic agents, are prepared by reacting 1-R1 -1,2-dihydro-2-oxo-5-PY-6-R-nicotinonitriles with hydroxylamine and are converted by reaction with polyphosphoric acid to the corresponding cardiotonically useful 1-R1 -3-amino-5-PY-6-R-2(1H)-pyridinones, where R1 is hydrogen, lower-alkyl and lower-hydroxyalkyl, R is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.
3-Amino-5-(pyridinyl)-2(1H)-pyridinones
-
, (2008/06/13)
Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting α-PY-β-(R1 R2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or α-PY-malonaldehyde (II') with α-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.
